1. Field of the Invention
The present invention relates to a method for producing L-3,4-dihydroxyphenylalanine (hereinafter referred to as L-DOPA). L-DOPA has been popularly used as for treating Parkinson's disease.
2. Description of the Background
Previously, L-DOPA has been produced synthetically starting from vanillin. In addition, other methods for producing L-DOPA, using an enzymes and microorganisms, have been investigated. For example JP-B 48-34237 (the term "JP-B" as used herein means an "examined Japanese patent publication") describes a method for producing L-DOPA from catechol, pyruvic acid and ammonium ion using .beta.-tyrosinase. JP-B 47-22275 describes a method for producing L-DOPA from catechol and L-serine and other amino acids also using .beta.-tyrosinase. JP-B 62-24076 describes a method for producing L-DOPA from dihydroxycinnamic acid and ammonium ions using ammonia lyase. JP-B 47-19033 and JP-B 47-14915 describe methods for producing L-DOPA from L-phenylalanine or L-tyrosine, using oxygenase. JP-B 58-18475 describes a method for producing L-DOPA from 3,4-dihydroxyphenylpyruvic acid using transaminase.
There are two types of L-DOPA crystals, monohydrated crystals and anhydrous crystals. Monohydrated crystals of L-DOPA are needle-like crystals, while anhydrous crystals of L-DOPA are tetragonal crystals. JP-B 49-41188 describes a method of purifying L-DOPA by crystallizing needle-like crystals of L-DOPA from an aqueous L-DOPA solution containing impurities at a low temperature not higher than 30.degree. C. followed by heating them at a temperature not lower than 30.degree. C. so as to convert them into tetragonal crystals by polymorphic transition and separating the thus-converted tetragonal crystals from the solution. According to this method, L-DOPA is crystallized as needle-like crystals whereby the color substances and other impurities that have been in the crude L-DOPA obtained in the production step are effectively removed. Afterwards, the needle-like crystals are separated and then converted into tetragonal crystals of pure L-DOPA by polymorphic transition.
JP-A 5-123177 (the term "JP-A" as used herein means an "unexamined published Japanese patent application") describes the production and accumulation of an extremely high concentration of L-DOPA by improving a method of producing L-DOPA which uses .beta.-tyrosinase. According to this method, L-DOPA is produced and accumulated in the reaction mixture at a concentration higher than the solubility of L-DOPA in the liquid. However, when the reaction is conducted at low temperatures, the crystals precipitated are monohydrated crystals and are thus difficult to separate and recover. On the other hand, when the reaction is conducted at high temperatures, anhydrous crystals of L-DOPA are precipitated. Unfortunately, many unfavorable side products are formed in the reaction system reducing the yield of crystals obtained. Accordingly, it is desirable to find a method of producing L-DOPA inexpensively and more efficiently than known conventional methods of producing L-DOPA.